Practice question

Without Wnt ligand, destruction complex remains constitutively active repressing signaling and preventing ectopic axes. Axin polymerizes with APC scaffolding GSK3beta and CK1alpha kinases, sequentially phosphorylating beta-catenin N-terminal Ser-Thr cluster Ser45,33,37,41. Phosphorylated beta-catenin binds beta-TrCP adaptor of SCF E3 ubiquitin ligase, polyubiquitinated, degraded in 26S proteasome, keeping cytoplasmic and nuclear pool low preventing TCF/LEF activation and target transcription. Upon Wnt binding Frizzled-Dishevelled recruits Axin to membrane via phosphorylated LRP5/6 intracellular PPPSP motifs, complex disassembles, beta-catenin accumulates and translocates to nucleus activating c-Myc, axis genes. Default off state critical.